Binding of thrombin-activated platelets to a fibrin scaffold through α(IIb)β₃ evokes phosphatidylserine exposure on their cell surface.
Binding of thrombin-activated platelets to a fibrin scaffold through α(IIb)β₃ evokes phosphatidylserine exposure on their cell surface.
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DOI：
10.1371/journal.pone.0055466
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Urano T
中科院分区：
文献类型：
--
作者：
Brzoska T;Suzuki Y;Mogami H;Sano H;Urano T
最近，通过采用活体共聚焦显微镜，我们证明血小板暴露的磷脂酰丝氨酸（PS）和纤维蛋白仅积聚在血栓的中心，而不是在其周围。为了解决血小板阴离子磷脂在血栓内的暴露如何受到调节的问题，采用了使用稀释的富含血小板血浆的体外实验，其中在血小板存在的情况下形成纤维蛋白网络，并使用共焦激光扫描显微镜分析了血小板表面的PS暴露。几乎所有血小板在用组织因子、凝血酶或离子霉素处理后都暴露于PS。阿加曲班消除了所有样品中的纤维蛋白网络形成，然而，血小板 PS 暴露仅在组织因子和凝血酶处理的样品中受到抑制，而在离子霉素处理的样品中则没有。 FK633（一种 αIIbβ3 拮抗剂）和细胞松弛素 B 会损害血小板与纤维蛋白支架的结合，并显着减少凝血酶引起的 PS 暴露。 Gly-Pro-Arg-Pro 酰胺不仅消除了纤维蛋白网络的形成，而且消除了血小板上的 PS 暴露，而不抑制血小板与纤维蛋白/纤维蛋白原的结合。这些结果表明，血小板中通过与刚性纤维蛋白网络结合而产生的由外向内信号对于凝血酶处理后的 PS 暴露至关重要。
Recently, by employing intra-vital confocal microscopy, we demonstrated that platelets expose phosphatidylserine (PS) and fibrin accumulate only in the center of the thrombus but not in its periphery. To address the question how exposure of platelet anionic phospholipids is regulated within the thrombus, an in-vitro experiment using diluted platelet-rich plasma was employed, in which the fibrin network was formed in the presence of platelets, and PS exposure on the platelet surface was analyzed using Confocal Laser Scanning Microscopy. Almost all platelets exposed PS after treatment with tissue factor, thrombin or ionomycin. Argatroban abrogated fibrin network formation in all samples, however, platelet PS exposure was inhibited only in tissue factor- and thrombin-treated samples but not in ionomycin-treated samples. FK633, an αIIbβ3 antagonist, and cytochalasin B impaired platelet binding to the fibrin scaffold and significantly reduced PS exposure evoked by thrombin. Gly-Pro-Arg-Pro amide abrogated not only fibrin network formation, but also PS exposure on platelets without suppressing platelet binding to fibrin/fibrinogen. These results suggest that outside-in signals in platelets generated by their binding to the rigid fibrin network are essential for PS exposure after thrombin treatment.
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